MAPT and Alzheimer disease: Extracellular amyloid plaques composed of neurotoxic Aβ aggregations, intracellular neurofibrillary tangles (NFTs) assembled by hyperphosphorylated tau protein, and UPS dysfunction unable to clear toxic or unwanted proteins that can cause neuroinflammation and eventually neuronal death, have all been hypothesized to play major roles in the pathogenesis of AD [26].